Angiotensin II (Ang II) as an important pathogenic factor, has been implicated in the pathogenesis of hypertension and associated renal injury, and inhibition of Ang II can reduce renal inflammation and exert renal protective effects. In the present study, we determine the infiltration of Th22 cells in kidney and serum IL-22 level in hypertensive renal injury, and explore the effects and mechanisms of a widely used angiotensin II type 1 receptor blocker irbesartan on Th22 cells infiltration and related renal injury. Hypertension was induced by administering 1.5 mg/kg Ang II subcutaneously daily in C57BL/6 mice for 28 days. The mice were additionally treated by irbesartan or amlodipine. Renal Th22 lymphocytes frequency was evaluated through flow cytometry, serum IL-22 was detected by ELISA, and renal histopathological changes were also detected. The levels of renal chemokines (CCL20, CCL22, CCL27) and serum proinflammatory factors (IL-1β, IL-6, TNF-α) were measured by ELISA. Renal expression of alpha-smooth muscle actin (α-SMA), Fibronectin (FN) and collagen I (Col I) were evaluated by western blot. Chemotaxis assay and co-culture assay were conducted to clarify the effect of irbesartan on Th22 cells chemotaxis and differentiation in vitro. Our results showed in Ang II-infused hypertension mice, irbesartan suppressed renal Th22 cells accumulation as well as CCL20, CCL22, CCL27 expression. Serum IL-22, IL-1β, IL-6 and TNF-α concentrations wasere also reduced, in addition to inhibited renal expression of α-SMA, FN and Col I. Irbesartan treatment lowered blood pressure, urinary protein and renal pathological damage. In vitro, irbesartan could abrogate the Th22 cells chemotaxis and differentiation, compared to control and amlodipine groups. Our study reveals a new pharmacological mechanism that irbesartan ameliorates inflammation and fibrosis in hypertensive renal injury induced by Ang II, maybe through inhibiting Th22 cells chemotaxis and infiltration, which provides a new theoretical basis and therapeutic target for hypertensive renal injury.

血管紧张素II（Ang II）作为重要的致病因素，已与高血压和相关的肾脏损伤的发病机制有关，抑制Ang II可以减少肾脏炎症并发挥肾脏保护作用。在本研究中，我们确定了高血压肾脏损伤中肾脏Th22细胞的浸润和血清IL-22的水平，并探讨了广泛使用的血管紧张素II 1型受体阻滞剂厄贝沙坦对Th22细胞浸润和相关肾脏损伤的作用和机制。每天在C57BL / 6小鼠中皮下注射1.5 mg / kg Ang II，持续28天，从而诱发高血压。另外用厄贝沙坦或氨氯地平治疗小鼠。通过流式细胞术评估肾Th22淋巴细胞的频率，通过ELISA检测血清IL-22，并且还检测肾组织病理学变化。用ELISA法测定肾趋化因子（CCL20，CCL22，CCL27）和血清促炎因子（IL-1β，IL-6，TNF-α）的水平。通过蛋白质印迹法评估α-平滑肌肌动蛋白（α-SMA），纤连蛋白（FN）和胶原蛋白I（Col I）的肾脏表达。进行了趋化性测定和共培养测定，以阐明厄贝沙坦对Th22细胞体外趋化性和分化的影响。我们的结果表明，在注入Ang II的高血压小鼠中，厄贝沙坦抑制了肾Th22细胞的蓄积以及CCL20，CCL22，CCL27的表达。血清IL-22，IL-1β，IL-6和TNF-α的浓度也降低，除了抑制了α-SMA，FN和Col I的肾脏表达。厄贝沙坦治疗还降低了血压，尿蛋白和肾脏病理损害。体外，与对照组和氨氯地平组相比，厄贝沙坦可以消除Th22细胞的趋化性和分化。我们的研究揭示了厄贝沙坦改善AngⅡ诱导的高血压肾损伤中炎症和纤维化的新药理机制，可能是通过抑制Th22细胞的趋化性和浸润，为高血压肾损伤提供了新的理论基础和治疗目标。